Many people think tuberculosis (TB) is a disease of the past. But, TB
is still a leading killer of young adults worldwide. Some 2 billion people
– one-third of the world's population – are infected with the TB
bacterium, M. tuberculosis. TB is a chronic bacterial infection.
It is spread through the air and usually infects the lungs, although other
organs are sometimes involved. Most persons that are infected with M.
tuberculosis harbor the bacterium without symptoms but many develop
active TB disease. Each year, 8 million people worldwide develop active TB
and 3 million die.

Is TB a problem in the United States?

In the United States, TB has re-emerged as a serious public health
problem. In 2001, based on provisional data reported to the U.S. Centers
for Disease Control and Prevention, the number of cases has decreased for
the ninth straight year to 15,991 cases of active TB (infection with
full-blown disease symptoms). This all-time low is due largely to improved
public health control measures. In addition to those with active TB,
however, an estimated 10 to 15 million people in the United States are
infected with M. tuberculosis without displaying symptoms (latent
TB) and about one in ten of these individuals will develop active TB at
some time in their lives.

Minorities are affected disproportionately by TB: 54 percent of active
TB cases in 1999 were among African-American and Hispanic people, with an
additional 20 percent found in Asians.

Cases of TB dropped rapidly in the 1940s and 1950s when the first
effective antibiotic therapies for TB were introduced. In 1985, however,
the decline ended and the number of active TB cases in the United States
began to rise again. Several forces, often interrelated, were behind TB's
resurgence:

The HIV/AIDS epidemic. People with HIV are particularly vulnerable
to turn infection with M. tuberculosis into active TB and are
also more sensitive to developing active TB when they are first infected
with the TB germ.

Increased numbers of foreign-born nationals from countries where
many cases of TB occur, such as Africa, Asia, and Latin America. TB
cases among those persons now living in the US account for nearly half
of the national total.

Increased poverty, injection drug use, and homelessness. TB
transmission is rampant in crowded shelters and prisons where people
weakened by poor nutrition, drug addiction, and alcoholism are exposed
to M. tuberculosis.

Failure of patients to take their prescribed antibiotics against TB
as directed.

Increased numbers of residents in long-term care facilities such as
nursing homes. Many develop active TB from infections with M.
tuberculosis that occurred much earlier in life because their
general health has declined. Other elderly people, especially those with
weak immune systems, become newly infected with M. tuberculosis
and can rapidly develop active TB.

TB is primarily an airborne disease. The disease is spread from person
to person in tiny microscopic droplets when a TB sufferer coughs, sneezes,
speaks, sings, or laughs. Only people with active disease are
contagious.

It usually takes lengthy contact with someone with active TB before a
person can become infected. On average, people have a 50 percent chance of
becoming infected with M. tuberculosis if they spend eight hours
a day for six months or 24 hours a day for two months working or living
with someone with active TB. However, people with TB who have been treated
with appropriate drugs for at least two weeks are no longer contagious and
do not spread the germ to others.

Adequate ventilation is the most important measure to prevent the
transmission of TB.

Between two to eight weeks after being infected with M.
tuberculosis, a person's immune system responds to the TB germ by
walling off infected cells. From then on the body maintains a standoff
with the infection, sometimes for years. Most people undergo complete
healing of their initial infection, and the bacteria eventually die off. A
positive TB skin test, and old scars on a chest x-ray, may provide the
only evidence of the infection.

If, however, the body's resistance is low because of aging, infections
such as HIV, malnutrition, or other reasons, the bacteria may break out of
hiding and cause active TB.

One in ten people that are infected with M. tuberculosis may
develop active TB at some time in their lives. The risk of developing
active disease is greatest in the first year after infection, but active
disease often does not occur until many years later.

Early symptoms of active TB can include weight loss, fever, night
sweats, and loss of appetite, or they may be vague and go unnoticed by the
affected individual. One in three patients with TB will die within weeks
to months if the disease is not treated. For the rest, their disease
either goes into remission (halts) or becomes chronic and more
debilitating with cough, chest pain, and bloody sputum.

Symptoms of TB involving areas other than the lungs vary, depending
upon the organ affected.

Doctors can identify most people infected with M. tuberculosis
with a skin test. They will inject a substance under the skin of the
forearm. If a red welt forms around the injection site within 72 hours,
the person may have been infected. This doesn't necessarily mean he or she
has active disease. Most people with previous exposure to M.
tuberculosis will test positive on the tuberculin test, as will some
people exposed to bacteria that are related to the TB germ.

If a person has an obvious reaction to the skin test, other methods can
help to show if the individual has active TB. In making a diagnosis,
doctors rely on symptoms and other physical signs, a person's history of
exposure to TB, and x-rays that may show evidence of M.
tuberculosis infection.

The doctor also will take sputum and other samples, to see if the TB bacteria
will grow in the lab. If bacteria are growing, this positive culture confirms
the diagnosis of TB. Because M. tuberculosis grows very slowly, it
can take four weeks to confirm the diagnosis. An additional two to three weeks
usually are n<eeded to determine which antibiotics the bacteria are susceptible
to.

With appropriate antibiotic treatment, TB can be cured in more than
nine out of ten patients.

Successful treatment of TB depends on close cooperation between the
patient and doctor and other health care workers. Treatment usually
combines several different antibiotic drugs which are given for at least
six months, sometimes for as long as 12 months.

Patients must take their medicine on time every day for the 6 to 12
months. Some TB patients stop taking their prescribed medicines because
they may feel better after only a couple of weeks of treatment. Another
reason they may stop taking their medicine is because TB drugs can have
unpleasant side effects.

If patients don't take all their medicine the way their doctor tells
them, they can become sick again and spread TB to their friends and
family. Additionally, when patients do not take all the drugs the doctor
has prescribed or skip times when they are supposed to take them, the TB
bacteria learn to outwit the TB antibiotics, and soon those medications no
longer work against the disease. If this happens, the person now has
resistant TB infection. Some patients have disease that is resistant to
two or more drugs. This is called multidrug-resistant TB or MDR-TB because
the TB germ, M. tuberculosis resists eradication with more than
drug. This form of TB is much more difficult to cure.

Treatment for MDR-TB often requires the use of special TB drugs, all of
which can produce serious side effects. To cure MDR-TB, patients may have
to take several antibiotics, at least three to which the bacteria still
respond, every day for up to two years. However, even with this treatment,
between four and six out of ten patients with MDR-TB will die, which is
the same as for patients with normal TB who do not receive treatment.

TB is largely a preventable disease. In the United States, doctors try
to identify persons infected with M. tuberculosis as early as
possible, before they have developed active TB. They will give a drug
called isoniazid (INH) to prevent the active disease. This drug is given
every day for 6 to 12 months. INH can cause hepatitis in a small
percentage of patients, especially those older than 35 years. A nurse may
watch the patients take their medicine to make sure all pills are
taken.

Hospitals and clinics can take precautions to prevent the spread of TB.
Precautions include using ultraviolet light to sterilize the air, special
filters, and special respirators and masks. Until they can no longer
spread the TB germs, TB patients in hospitals should be isolated in
special rooms with controlled ventilation and airflow.

In those parts of the world where the disease is common, the World
Health Organization (WHO) recommends that infants receive a vaccine called
BCG made from a live weakened bacterium related to M.
tuberculosis. BCG vaccine prevents M. tuberculosis from
spreading within the body, thus preventing TB from developing.

However, the vaccine has its drawbacks. It does not protect adults very
well against TB. In addition, BCG interferes with the TB skin test,
showing a positive skin test reaction in people who have received BCG
vaccine. In countries where BCG vaccine is used, the ability of the skin
test to identify persons that are infected with M. tuberculosis
is limited. Because of these limitations, more effective vaccines are
needed and BCG is not recommended for general use in the United
States.

How is M. tuberculosis
infection different in people with HIV infection?

The World Health Organization (WHO) estimates that 10 million people
worldwide are infected with the M. tuberculosis bacterium and HIV
virus at the same time. The primary cause of death in these patients is
from TB, not AIDS. In the United States, it is estimated that about 2 out
of ten persons who have TB are also infected with HIV.

One of the first indications that a person is infected with HIV may be
that he or she suddenly develops TB. This form of TB often occurs in areas
outside the lungs, particularly when the patient is in the later stages of
AIDS.

In the United States, it is much more likely for persons infected with
M. tuberculosis and HIV to develop active TB than it is for
someone that is only infected with M. tuberculosis. However, TB
disease can be prevented and cured, even in people with HIV infection.

People with MDR-TB that are also infected with HIV appear to have a
more rapid and deadly disease course than do those patients with MDR-TB
who are otherwise healthy. If no medicines are available for these
patients as many as eight out of ten may die, often within months of
diagnosis.

Diagnosing TB in HIV-infected people is often difficult. HIV infected
patients frequently have disease symptoms similar to those of TB, and may
not react to the standard TB skin test because their immune system does
not work properly. X-rays, sputum tests, and physical exams may also fail
to provide evidence of infection with M. tuberculosis in
HIV-infected individuals.

The National Institute of Allergy and Infectious Diseases (NIAID) leads
TB research at the National Institutes of Health. NIAID supports not only
studies to better understand how M. tuberculosis infects and
causes disease in humans but also how the human immune system responds to
it. This research will help to develop new tools to diagnose TB, find
better vaccines, and new medicines against TB. Below are some important
advances that have been made in TB research:

Diagnosis: Potential new tests to speed the diagnosis
of TB from four weeks to two days; differences found in the DNA of M.
tuberculosis and the bacterium used in the BCG vaccine may lead to a
test to tell the difference between people who really have TB and those
who only react to previous BCG vaccination.

Treatment: Discovery of the molecules responsible for
drug resistance, knowledge that will help doctors quickly select the best
treatments for their patients; a new drug under study can be taken less
often to help patients comply with their treatment regimen.

Vaccines: More than 90 vaccine candidates have been
developed and tested in animals.

Training: An innovative TB telemedicine program where
NIAID physicians share their expertise with doctors in Texas; an urban
program in Washington, DC where NIAID TB clinical trials are made more
accessible to inner city patients; international collaborations with
investigators to help them build research capabilities, and carry out
research that will benefit populations in countries where TB disease is
most common.

Recognizing that disease knows no borders, NIAID has developed a global
TB research agenda. A concerted global effort will require collaborations
with sister agencies and other organizations with similar goals such as
the Global Alliance for TB Drug Development and the STOP TB initiative, as
well as partnerships with governments and scientists from countries where
the burden of tuberculosis is greatest.

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